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Complications of chronic kidney disease (CKD) impair cardiovascular health and quality of life. Health-related QoL (HRQoL) is influenced by cultural perspectives, social environment and health behaviors that vary across countries with varying income. Therefore, present review aims to report HRQoL in people with CKD and factors influencing HRQoL in low- and middle-income countries (LMICs). Fifty relevant studies were reviewed following literature search in Cochrane Library, PubMed, Google Scholar and CINAHL databases using key words: quality of life, CKD, and LMICs. HRQoL was poor in people with CKD compared with healthy individuals. QoL was positively influenced by younger age, male gender, employment and higher socioeconomic status. Presence of comorbidities, anemia and low hemoglobin levels were associated with poor QoL. Intrinsic and extrinsic factors influencing HRQoL were similar in people with CKD in LMICs and high-income countries (HICs). However, overall HRQoL and mental-health scores were lower with reference to HICs. Therefore, a multipronged approach designed towards prevention of kidney disease, early detection and management to delay end-stage kidney disease through health education, modification of risk factors, accessible and affordable comprehensive management of kidney disease is necessary. In resource constrained settings of LMIC, strategic investment in planning and implementation of prophylactic and monitoring measures will help to reduce huge financial costs necessary for management and improvement of HRQoL of people with CKD.

Takayasu arteritis (TAK) is an autoimmune disease majorly affecting young females. It alters the vascular wall, resulting in stenosis, occlusion, or dilatation. It has no distinct clinical manifestation. Here, we present the case of an 18-year-old girl who presented with generalized tonic-clonic seizure and hypoxia. Blood investigations showed deranged urea and creatinine values. Computed tomography angiography revealed bilateral artery occlusion, decreased kidney size, and pulmonary artery dilatation, confirming generalized vascular disease that caused hypertension and ischemic nephropathy in the patient. Our case represents a rare autoimmune disease, leading to pulmonary hypertension and renal artery stenosis. TAK should be considered as a differential diagnosis in young female patients presenting with pulmonary as well as renal signs and symptoms, especially if there is discrepancy in blood pressure levels in all limbs. Case summary- An 18yr old girl presented with generalized tonic-clonic seizure and hypoxia. Blood investigations showed deranged urea and creatinine values. CT angiography revealed occlusion of bilateral arteries along with decreased size of both the kidneys. It also revealed pulmonary artery dilatation and hence generalized vascular disease was confirmed which caused hypertension along with ischaemic nephropathy in the patient. Discussion- Our case represents a rare autoimmune disease leading to pulmonary hypertension and renal artery stenosis. Whenever young female patients present with associated pulmonary as well as renal signs and symptoms, Takayasu arteritis should be considered as a differential diagnosis,especially if there is discrepency in blood pressure levels in all four limbs.

This paper analyses the reconfiguration of the relationship between technological apparatus and our mental lifeworld. Technological network apparatus, particularly algorithmic networks are absorbing large domains of our life into themselves. In the process, our sense of self-identity has become fragile. We keep feeling disoriented by the overload of technological acceleration in our life in form of messages, notifications, and new methods of algorithmic monitoring of our life. Our sensory perception of reality has been hegemonised by intelligent machines. In response, the mental-health discourse identifies new mental-illnesses and their treatment procedures. However, the mental-health discourse functions on certain underlying philosophical assumptions which limit its ability to understand the contemporary real mental-problems faced by human beings. It gets trapped in its own logic. While claiming to bring the patient back into normality, it only traps humans further in the processes of human mechanisation. This paper highlights some of these issues and introspects new ways of understanding the current problem by going beyond the mental-health discourse.

This paper critically evaluates the impact of Artificial Intelligence-based automation on the nature of work. Contrary to the conventional belief that automation replaces human-labour, or that it makes the human-labour easier, this paper argues that neither of these are true. The paper proposes an understanding where the work is neither replaced nor made easy, it only changes its form. In the process of changing its form, the new work-regime radically transforms the worker’s relations with the production process and the machine, in effect, encompassing all aspects of a worker’s time and reality.

The Evening Complex (EC), composed of the DNA binding protein LUX ARRHYTHMO (LUX) and two additional proteins EARLY FLOWERING 3 (ELF3) and ELF4, is a transcriptional repressor complex and a core component of the plant circadian clock. In addition to maintaining oscillations in clock gene expression, the EC also participates in temperature and light entrainment, acting as an important environmental sensor and conveying this information to growth and developmental pathways. However, the molecular basis for EC DNA binding specificity and temperature-dependent activity were not known. Here, we solved the structure of the DNA binding domain of LUX in complex with DNA. Residues critical for high-affinity binding and direct base readout were determined and tested via site-directed mutagenesis in vitro and in vivo. Using extensive in vitro DNA binding assays of LUX alone and in complex with ELF3 and ELF4, we demonstrate that, while LUX alone binds DNA with high affinity, the LUX–ELF3 complex is a relatively poor binder of DNA. ELF4 restores binding to the complex. In vitro, the full EC is able to act as a direct thermosensor, with stronger DNA binding at 4 °C and weaker binding at 27 °C. In addition, an excess of ELF4 is able to restore EC binding even at 27 °C. Taken together, these data suggest that ELF4 is a key modulator of thermosensitive EC activity., Proceedings of the National Academy of Sciences of the United States of America, 117 (12), ISSN:0027-8424, ISSN:1091-6490

International audience; Use of nanonized curcumin-whey protein (CWP) composite particles as Pickering stabilizers are an attractive strategy due to their edibility and natural origin. This study aimed to examine the effect of physico-chemical conditions (pH, ionic strength, protein form) during the formation of CWP composite nanoparticles on their physico-chemical characteristics (size, surface charge, morphology) and further their Pickering ability by influencing their aptitude to stabilize oil/water interfaces. Our study demonstrated that, to favor the protein-curcumin interactions and to improve the particle characteristics (smaller size, monodispersity), one should increase the accessibility of hydrophobic moiety of proteins (denaturation) and control ionic strength. Increasing the concentration of the CWP composite nanoparticles decreased size and polydispersity enhancing emulsion stability. Use of these CWP composite nanoparticles in food products with high ionic strength will tend to flocculation and thereby emulsions destabilization. This work allows for a better understanding of the role of physico-chemical conditions on the formation of CWP composite nanoparticles and thereof their oil/water interfacial activity.

Significance Circadian gene expression oscillates over a 24-h period and regulates many genes critical for growth and development in plants. A key component of the circadian clock is the Evening Complex (EC), a transcriptional repressor complex that contains the proteins LUX ARRHYTHMO, EARLY FLOWERING 3, and EARLY FLOWERING 4 (ELF4). By repressing the expression of genes such as PHYTOCHROME INTERACTING FACTOR4 (PIF4), the EC reduces elongation growth. At warmer temperatures, EC activity is lost, promoting thermomorphogenesis via PIF4 expression. The molecular mechanisms underlying EC activity are not well understood. Here, we combined structural studies with extensive in vitro assays to determine the molecular mechanisms of the temperature-dependent EC binding to DNA and demonstrate the critical role of ELF4 in this activity., The Evening Complex (EC), composed of the DNA binding protein LUX ARRHYTHMO (LUX) and two additional proteins EARLY FLOWERING 3 (ELF3) and ELF4, is a transcriptional repressor complex and a core component of the plant circadian clock. In addition to maintaining oscillations in clock gene expression, the EC also participates in temperature and light entrainment, acting as an important environmental sensor and conveying this information to growth and developmental pathways. However, the molecular basis for EC DNA binding specificity and temperature-dependent activity were not known. Here, we solved the structure of the DNA binding domain of LUX in complex with DNA. Residues critical for high-affinity binding and direct base readout were determined and tested via site-directed mutagenesis in vitro and in vivo. Using extensive in vitro DNA binding assays of LUX alone and in complex with ELF3 and ELF4, we demonstrate that, while LUX alone binds DNA with high affinity, the LUX–ELF3 complex is a relatively poor binder of DNA. ELF4 restores binding to the complex. In vitro, the full EC is able to act as a direct thermosensor, with stronger DNA binding at 4 °C and weaker binding at 27 °C. In addition, an excess of ELF4 is able to restore EC binding even at 27 °C. Taken together, these data suggest that ELF4 is a key modulator of thermosensitive EC activity.

The Evening Complex (EC), composed of the DNA-binding protein LUX ARRHYTHMO (LUX) and two additional proteins, EARLY FLOWERING 3 (ELF3) and ELF4, is a transcriptional repressor complex and a core component of the plant circadian clock. In addition to maintaining oscillations in clock gene expression, the EC also participates in temperature and light entrainment and regulates important clock output genes such asPHYTOCHROME INTERACTING FACTOR 4(PIF4), a key transcription factor involved in temperature dependent plant growth. These properties make the EC an attractive target for altering plant development through targeted mutations to the complex. However, the molecular basis for EC function was not known. Here we show that binding of the EC requires all three proteins and that ELF3 decreases the ability of LUX to bind DNA whereas the presence of ELF4 restores interaction with DNA. To be able to manipulate this complex, we solved the structure of the DNA-binding domain of LUX bound to DNA. Using structure-based design, a LUX variant was constructed that showed decreasedin vitrobinding affinity but retained specificity for its cognate sequences. This designed LUX allele modulates hypocotyl elongation and flowering. These results demonstrate that modifying the DNA-binding affinity of LUX can be used to titrate the repressive activity of the entire EC, tuning growth and development in a predictable manner.Significance StatementCircadian gene expression oscillates over a 24 hr. period and regulates many genes critical for growth and development. In plants, the Evening Complex (EC), a three-protein repressive complex made up of LUX ARRYTHMO, EARLY FLOWERING 3 and EARLY FLOWERING 4, acts as a key component of the circadian clock and is a regulator of thermomorphogenic growth. However, the molecular mechanisms of complex formation and DNA-binding have not been identified. Here we determine the roles of each protein in the complex and present the structure of the LUX DNA-binding domain in complex with DNA. Based on these data, we used structure-based protein engineering to produce a version of the EC with alteredin vitroandin vivoactivity. These results demonstrate that the EC can be modified to alter plant growth and development at different temperatures in a predictable manner.

Eco-friendly biosynthetic approach for silver nanoparticles production using plant extracts is an exciting advancement in bio-nanotechnology and has been successfully attempted in nearly 41 plant species. However, an established model plant system for systematically unraveling the biochemical components required for silver nanoparticles production is lacking. Here we used Arabidopsis thaliana as the model plant for silver nanoparticles biosynthesis in vitro. Employing biochemical, spectroscopic methods, selected mutants and over-expressor plants of Arabidopsis involved in pleotropic functions and sugar homeostasis, we show that carbohydrates, polyphenolics and glyco-proteins are essential components which stimulated silver nanoparticles synthesis. Using molecular genetics as a tool, our data enforces the requirement of sugar conjugated proteins as essentials for AgNPs synthesis over protein alone. Additionally, a comparative analysis of AgNPs synthesis using the aqueous extracts of some of the plant species found in a brackish water ecosystem (Gracilaria, Potamogeton, Enteromorpha and Scendesmus) were explored. Plant extract of Potamogeton showed the highest potential of nanoparticles production comparable to that of Arabidopsis among the species tested. Silver nanoparticles production in the model plant Arabidopsis not only opens up a possibility of using molecular genetics tool to understand the biochemical pathways and components in detail for its synthesis.

The study evaluates in vivo antimalarial activity of arteether and garlic pearl oil combination in Plasmodium berghei -infected mouse model of malaria. 72 h (Day 3) post infection, at 2–4% parasitemia, mice were treated with single dose intramuscular injection of α-β arteether, at 750 μg, in combination with three 100 μL oral doses of garlic pearl oil on Day 3, Day 4 and Day 5. Following the treatment, 100% protection and survival of mice were observed. Inhibition of parasitemia in combination treated animals and protection during recrudescence interval of α-β arteether monotherapy was observed in Giemsa-stained blood smears. In addition, a striking increase in anti-parasite antibody IgG contributing protective immunity during the recrudescence phase was observed. These results correlate with western blot analysis, where sera from the recrudescence stage and later period of arteether and garlic oil combination treated animals found to interact with several parasite specific proteins as compared to controls. The present approach shows that arteether and garlic pearl oil combination provides complete protection in P. berghei -infected mice. Thus, for the first time, garlic pearl oil appears to be an ideal antimalarial candidate in artemisinin combination therapy.

The goal of this paper is analyzing the performance of a standalone PV with battery energy storage system (BESS) and diesel generator (DG) as a backup available in a rural area of Khurda district in Odisha, India considering the average hourly solar irradiation, ambient temperature and load profile of that location which will help the small remote village avail electricity. In this paper the dynamic models of hybrid system as well as cycle charging dispatch control strategy are considered. The timed performances of the battery energy storage system with a standalone solar PV and diesel generator system is determined so that the hybrid system will be sufficient to feed the load demand and decrease the overall maintenance cost of the system by reducing the cost of fuel for the diesel generator. Moreover such models can be used in the assessment, sizing, control and performance evaluation of hybrid solar PV, diesel generator and battery storage system.

In The ability to visualize our thoughts has always fascinated us. Even more intriguing is the subject of making a computer able to visualize those thoughts, just by understanding the human language. In this paper, a text to scene generation system is proposed for the educational domain where a basic Newtonian physics problem is conveyed to the system in natural language and the scene depicting the problem is generated and displayed to the user. The paper describes the implementation of the system as well as the results obtained. It is based on the integration of advances in NLP and computer graphics technology to generate a virtual environment. It makes it easier for students to visualize the problems and also helps teachers in explaining better. General Terms Your general terms must be any term which can be used for general classification of the submitted material such as Pattern Recognition, Security, Algorithms et. al.

Simon J. Conn (simon.conn@unisa.edu.au); International audience; Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non-canonical RNAs that arise through a form of alternative splicing (AS) called back-splicing. These single-stranded, covalently-closed circRNA molecules have been identified in all eukaryotic kingdoms of life(1), yet their functions have remained elusive. Here, we report that circRNAs can be used as $bona\ fide$ biomarkers of functional, exon-skipped AS variants in $Arabidopsis$, including in the homeotic MADS-box transcription factor family. Furthermore, we demonstrate that circRNAs derived from exon 6 of the SEPALLATA3 (SEP3) gene increase abundance of the cognate exon-skipped AS variant (SEP3.3 which lacks exon 6), in turn driving floral homeotic phenotypes. Toward demonstrating the underlying mechanism, we show that the SEP3 exon 6 circRNA can bind strongly to its cognate DNA locus, forming an RNA:DNA hybrid, or R-loop, whereas the linear RNA equivalent bound significantly more weakly to DNA. R-loop formation results in transcriptional pausing, which has been shown to coincide with splicing factor recruitment and AS(2-4). This report presents a novel mechanistic insight for how at least a subset of circRNAs probably contribute to increased splicing efficiency of their cognate exon-skipped messenger RNA and provides the first evidence of an organismal-level phenotype mediated by circRNA manipulation.

Curcumin is one of the principle bioactive compounds used in the ayurvedic medicine system that has the history of over 5000 years for human use. Curcumin an "Indian Gold" is used to treat simple ailments like the common cold to severe life threatening diseases like cancer, and HIV. Though its contribution is immense for the health protection and disease prevention, its clinical use is limited due to its susceptible nature to alkaline pH, high temperature, presence of oxygen and light. Hence it becomes extremely difficult to maintain its bioactivity during processing, storage and consumption. Recent advancements in the application of nanotechnology to curcumin offer an opportunity to enhance its stability, bioactivity and to overcome its pharmacokinetic mismatch. This in turn helps to bridge the gaps that exist between its bench top research data to its clinical findings. Among the various types of nano/micro delivery systems, lipid based delivery systems are well studied and are the best suited delivery systems to enhance the stability and pharmacokinetic profile of curcumin both for pharma and the food application. In the current review, effort will be made to recapitulate the work done in the past to use lipid based delivery systems (liposomes, solid lipid nanoparticles, and emulsions) to enhance the application of curcumin for health promotion and disease prevention. Further, future prospects for the utilization of these lipid-based delivery systems will be discussed in detail.

The study evaluates in vivo antimalarial activity of arteether and garlic pearl oil combination in Plasmodium berghei-infected mouse model of malaria. 72 h (Day 3) post infection, at 2–4% parasitemia, mice were treated with single dose intramuscular injection of α-β arteether, at 750 μg, in combination with three 100 μL oral doses of garlic pearl oil on Day 3, Day 4 and Day 5. Following the treatment, 100% protection and survival of mice were observed. Inhibition of parasitemia in combination treated animals and protection during recrudescence interval of α-β arteether monotherapy was observed in Giemsa-stained blood smears. In addition, a striking increase in anti-parasite antibody IgG contributing protective immunity during the recrudescence phase was observed. These results correlate with western blot analysis, where sera from the recrudescence stage and later period of arteether and garlic oil combination treated animals found to interact with several parasite specific proteins as compared to controls. The present approach shows that arteether and garlic pearl oil combination provides complete protection in P. berghei-infected mice. Thus, for the first time, garlic pearl oil appears to be an ideal antimalarial candidate in artemisinin combination therapy., Graphical abstract fx1, Highlights • Garlic pearl oil enhanced antimalarial activity of α-β arteether. • Garlic pearl oil and α-β arteether combination effectively evaded recrudescence. • Garlic pearl oil and α-β arteether combination may elicit immunomodulatory effect. • This combination therapy resulted in a striking increase in anti-parasite antibody.

Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure during metaphase. More regional chromatin conformations have also been reported, including topologically associated domains encompassing mega-bases of DNA and local chromatin loops formed by kilo-bases of DNA. In this review, we discuss the changes in chromatin conformation taking place between somatic and meiotic cells, with a special focus on the establishment of a proteinaceous structure, called the chromosome axis, at the beginning of meiosis. The chromosome axis is essential to support key meiotic processes such as chromosome pairing, homologous recombination, and balanced chromosome segregation to transition from a diploid to a haploid stage. We review the role of the chromosome axis in meiotic chromatin organization and provide a detailed description of its protein composition. We also review the con served and distinct roles between species of axis proteins in meiotic recombination, which is a major factor contributing to the creation of genetic diversity and genome evolution. Finally, we discuss situations where the chromosome axis is deregulated and evaluate the effects on genome integrity and the consequences from protein deregulation in meiocytes exposed to heat stress, and aberrant expression of genes encoding axis proteins in mammalian somatic cells associated with certain types of cancers